In the past years, we have developed the methodology allowing the study of the expression of the thyroglobulin gene in mammals. Thyroglobulin synthesizing polysomes and thyroglobulin messenger RNA have been characterized and a thyroglobulin cDNA has been prepared. Taking advantage of these studies, we intend to investigate the molecular mechanisms involved in the regulation of the thyroglobulin gene. The study will be divided in the following two sections: 1. Study of the control by thyrotropin (TSH) of thyroglobulin synthesis. Both transcriptional and translational control will be studied in the bovine thyroid incubated or cultured in vitro. 2. Study of genetic defects of thyroglobulin synthesis in hereditary congenital goiters. Preliminary study of such a disorder in the goat have shown that it is associated with an abnormal subcellular distribution of thyroglobulin mRNA sequences. This study will be extended and similar cases occurring in the human will be investigated. The principal methodology which will be used is cDNA-RNA hybridizations, characterization of both ribo and deoxy-ribonucleic acid sequences will be required. The proposed study should lead to better understanding of the mechanisms involved in normal as well as in pathological expression of the thyroglobulin gene.